Hematopoietic activity of a stromal cell transmembrane protein containing epidermal growth factor-like repeat motifs
Hematopoietic activity of a stromal cell transmembrane protein containing epidermal growth factor-like repeat motifs
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DOI：
10.1073/pnas.94.8.4011
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发表时间：
1997-04-15
影响因子：
11.1
通讯作者：
Lemischka, IR
中科院分区：
文献类型：
--
作者：
Moore, KA;Pytowski, B;Lemischka, IR
原始造血干细胞与体内离散的微环境密切相关。这些“利基”被认为提供了调节干细胞分化和自我更新的分子信号。我们通过建立一个广泛的基质细胞系小组，将胎肝微环境解剖成不同的细胞成分。一种特殊的细胞系在体外培养期间保持干细胞的重新繁殖。一种消减克隆策略已经产生了一种编码细胞表面糖蛋白的cDNA，该糖蛋白在基质细胞系中具有受限的表达模式。该分子以前被确认为Delta样/前脂肪细胞因子-1，包含与Noch/Delta/Serrate蛋白质家族相关的表皮生长因子样重复序列。我们研究了该分子在造血干/祖细胞调控中的潜在作用。我们发现，Delta样蛋白通过促进增殖的“鹅卵石区域”的形成，在纯化的干细胞上显示出活性。这些鹅卵石区域既有原始的高增殖潜能祖细胞，也有体内重新繁殖的干细胞。
Primitive hematopoietic stem cells are closely associated with discrete in vivo microenvironments. These ''niches'' are thought to provide the molecular signals that mediate stem cell differentiation and self-renewal. We have dissected the fetal liver microenvironment into distinct cellular components by establishing an extensive panel of stromal cell lines. One particular cell line maintains repopulating stem cells for prolonged in vitro culture periods. A subtraction cloning strategy has yielded a cDNA that encodes a cell surface glycoprotein with a restricted pattern of expression among stromal cell lines. This molecule, previously identified as delta-like/preadipocyte factor-1, contains epidermal growth factor-like repeats that are related to those in the notch/delta/serrate family of proteins. We have investigated the potential role of this molecule in hematopoietic stem/progenitor cell regulation. We show that the delta-like protein displays activity on purified stem cells by promoting the formation of ''cobblestone areas'' of proliferation. These cobblestone areas contain both primitive high-proliferative potential progenitors and in vivo repopulating stem cells.